Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules

Liu, Yanjun; Wang, Hao; Zhao, Jian; Ma, Jing; Wei, Lixin; Wu, Shaofang; Xie, Tingting; Shen, Feng; Trojan, Jerzy; Habib, Nagy; Anthony, Donald D.; Wu, Mengchao; Guo, Yajun

doi:10.1038/sj.cgt.7700137

Cited by 17 publications

(13 citation statements)

References 22 publications

(41 reference statements)

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“…Several antisense strategies designed to inhibit immunosuppressive gene expression in tumor cells have been studied. Vaccination with tumor cells treated with antisense genes or oligonucleotides directed against insulin-like growth factor-1 (IGF-1) and transforming growth factor-ß (TGF-ß) have resulted in immune-mediated tumor regression in a number of animal models [19,35,40,75]. TGF-ß is a known immunosuppressive cytokine [22] and promoting antitumor immunity by blocking TGF-ß expression makes logical sense.…”

Section: Preclinical Studiesmentioning

confidence: 99%

Cancer Immunogene Therapy: A Review

Parney¹,

Chang²

2003

J Biomed Sci

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Although immunotherapy has long held out promise as a specific, potent approach to cancer therapy, clinical applications have been unrewarding to date. However, advances in gene transfer technology and basic immunology have opened new avenues to stimulate antitumor immune responses including immunogene therapy. Many different approaches to immunogene therapy have been identified. These include transferring genes encoding proinflammatory proteins to tumor cells, suppressing immunosuppressive gene expression, and transferring proinflammatory genes and/or tumor antigen genes to professional antigen-presenting cells. In some cases, genes are transferred to tumor or antigen-presenting cells in situ. In others, gene transfer is performed ex vivo as part of preparing an anticancer vaccine. We discuss the underlying approach, relative success, and clinical application of various cancer immunogene therapy strategies, paying particular attention to immunogene therapy vaccines. Large numbers of preclinical studies have been reported, but only scattered clinical trial results have appeared in the literature. Although very successful preclinically, the ideal cancer immunogene therapy approach remains to be determined and will likely vary with tumor type. Clinical impact may be improved in the future as treatment protocols are refined.

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Section: Preclinical Studiesmentioning

confidence: 99%

Cancer Immunogene Therapy: A Review

Parney¹,

Chang²

2003

J Biomed Sci

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“…L'absence de cette protéine membranaire pourrait expliquer la réponse partielle du traitement avec les ARN anti IGF-I. Très récemment, l'approche ARN antisens anti IGF-I a été couplée à l'expression de la molécule B7.1 afin d'obtenir un effet anti-tumoral [20]. Les cellules murines d'hépatomes et de carcinomes du côlon, du fait de leur faible immunogénicité, induisent le développement de tumeurs chez des souris nude, scid et syngéniques [20].…”

Section: Le Ligand Igf-i Et Les Tumeursunclassified

“…Très récemment, l'approche ARN antisens anti IGF-I a été couplée à l'expression de la molécule B7.1 afin d'obtenir un effet anti-tumoral [20]. Les cellules murines d'hépatomes et de carcinomes du côlon, du fait de leur faible immunogénicité, induisent le développement de tumeurs chez des souris nude, scid et syngéniques [20]. L'expression de l'ARN antisens anti IGF-I et de la protéine B7.1 dans ces cellules (par double transfection) a permis de disposer d'un vaccin cellulaire provoquant l'éradication de tumeurs préexistantes de même origine dans des modèles de souris syngéniques [20].…”

Section: Le Ligand Igf-i Et Les Tumeursunclassified

“…Les cellules murines d'hépatomes et de carcinomes du côlon, du fait de leur faible immunogénicité, induisent le développement de tumeurs chez des souris nude, scid et syngéniques [20]. L'expression de l'ARN antisens anti IGF-I et de la protéine B7.1 dans ces cellules (par double transfection) a permis de disposer d'un vaccin cellulaire provoquant l'éradication de tumeurs préexistantes de même origine dans des modèles de souris syngéniques [20]. Afin de démontrer le rôle fondamental joué par la réponse immunitaire dans l'éradication des tumeurs chez ces souris syngéniques, des expériences similaires ont été effectuées chez des souris immunodéprimées (scid et nude).…”

Section: Le Ligand Igf-i Et Les Tumeursunclassified

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Thérapies antisens dirigées contre le récepteur de l’IGF-I

François

Trojan

2001

Med Sci (Paris)

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“…The replicative adenovirus we used has previously been constructed in our lab in which E1A and E1B 19 K proteins were expressed from CAG and CMV promoters, respectively, and E1B 55 K and E3 genes were deleted (formerly AdCALE1AL; we call it AdREP hereafter). 6 We found that Hepa 1-6 cells (a poorly immunogenic mouse hepatoma cell line derived from C57BL/6 mice) (ATCC, Manassa, VA, USA) 7 is highly sensitive to adenovirus infection and susceptible to viral replication, progeny production and cytopathic effect (CPE), although slightly less permissive as compared to a human hepatoma cell line HuH-7 as a control. Thus, more than 95% of Hepa 1-6 and HuH-7 cells were stained with x-gal when infected with adenovirus expressing b-galactosidase (AdLacZ) 6 at a multiplicity of infection (MOI) of 10 and 3, respectively (data not shown).…”

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confidence: 99%

Enhanced antitumor effect of combined replicative adenovirus and nonreplicative adenovirus expressing interleukin-12 in an immunocompetent mouse model

et al. 2003

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For cancer gene therapy, replicative adenovirus is a promising vector to overcome low infectivity and poor gene delivery of nonreplicative adenovirus in vivo, but its therapeutic efficacy is still unsatisfactory because of the limited spread of replicative virus in a solid tumor. Therefore, the combined therapy with other antitumor agents may be necessary. Nonreplicative adenovirus expressing a therapeutic gene may be a promising candidate because E1 proteins expressed by replicative adenovirus would render nonreplicative adenovirus replicative, augmenting a transgene expression. In this study, we first found that mouse hepatoma Hepa 1-6 cells were permissive for the replication and cytopathic effect of human adenovirus, which enabled us to examine the potential of combined replicative adenovirus and nonreplicative adenovirus expressing an immunostimulator in an immunocompetent mouse-syngeneic Hepa 1-6 tumor model. Nonreplicative adenovirus expressing interleukin-12 (AdIL-12) was used as a model. In vitro coinfection of two adenoviruses produced higher concentrations of IL-12 than infection of AdIL-12 alone in this cell line. In vivo experiments with Hepa 1-6 tumors in syngeneic immunocompetent C57BL/6 mice showed higher concentrations of serum IL-12 and greater therapeutic efficacy in the combination therapy than infection of either adenovirus. These data indicate that the combination of replicative adenovirus and nonreplicative adenovirus expressing an immunostimulator appears to be very efficacious for cancer gene therapy.

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Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules

Cited by 17 publications

References 22 publications

Cancer Immunogene Therapy: A Review

Cancer Immunogene Therapy: A Review

Thérapies antisens dirigées contre le récepteur de l’IGF-I

Enhanced antitumor effect of combined replicative adenovirus and nonreplicative adenovirus expressing interleukin-12 in an immunocompetent mouse model

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